6wth
From Proteopedia
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| - | ==== | + | ==Full-length human ENaC ECD== |
| - | <StructureSection load='6wth' size='340' side='right'caption='[[6wth]]' scene=''> | + | <StructureSection load='6wth' size='340' side='right'caption='[[6wth]], [[Resolution|resolution]] 3.06Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id= OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[6wth]] is a 7 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6WTH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6WTH FirstGlance]. <br> |
| - | </td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.06Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6wth FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6wth OCA], [https://pdbe.org/6wth PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6wth RCSB], [https://www.ebi.ac.uk/pdbsum/6wth PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6wth ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Disease == | ||
| + | [https://www.uniprot.org/uniprot/SCNNA_HUMAN SCNNA_HUMAN] Idiopathic bronchiectasis;Generalized pseudohypoaldosteronism type 1. The disease is caused by mutations affecting the gene represented in this entry. The degree of channel function impairment differentially affects the renin-aldosterone system and urinary Na/K ratios, resulting in distinct genotype-phenotype relationships in PHA1 patients. Loss-of-function mutations are associated with a severe clinical course and age-dependent hyperactivation of the renin-aldosterone system. This feature is not observed in patients with missense mutations that reduce but do not eliminate channel function. Markedly reduced channel activity results in impaired linear growth and delayed puberty (PubMed:18634878). The disease is caused by mutations affecting the gene represented in this entry. | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/SCNNA_HUMAN SCNNA_HUMAN] Sodium permeable non-voltage-sensitive ion channel inhibited by the diuretic amiloride. Mediates the electrodiffusion of the luminal sodium (and water, which follows osmotically) through the apical membrane of epithelial cells. Controls the reabsorption of sodium in kidney, colon, lung and sweat glands. Also plays a role in taste perception. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The molecular bases of heteromeric assembly and link between Na(+) self-inhibition and protease-sensitivity in epithelial sodium channels (ENaCs) are not fully understood. Previously, we demonstrated that ENaC subunits - alpha, beta, and gamma - assemble in a counterclockwise configuration when viewed from outside the cell with the protease-sensitive GRIP domains in the periphery (Noreng et al., 2018). Here we describe the structure of ENaC resolved by cryo-electron microscopy at 3 A. We find that a combination of precise domain arrangement and complementary hydrogen bonding network defines the subunit arrangement. Furthermore, we determined that the alpha subunit has a primary functional module consisting of the finger and GRIP domains. The module is bifurcated by the alpha2 helix dividing two distinct regulatory sites: Na(+) and the inhibitory peptide. Removal of the inhibitory peptide perturbs the Na(+) site via the alpha2 helix highlighting the critical role of the alpha2 helix in regulating ENaC function. | ||
| + | |||
| + | Molecular principles of assembly, activation, and inhibition in epithelial sodium channel.,Noreng S, Posert R, Bharadwaj A, Houser A, Baconguis I Elife. 2020 Jul 30;9:e59038. doi: 10.7554/eLife.59038. PMID:32729833<ref>PMID:32729833</ref> | ||
| + | |||
| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 6wth" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Ion channels 3D structures|Ion channels 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: | + | [[Category: Mus musculus]] |
| + | [[Category: Baconguis I]] | ||
| + | [[Category: Bharadwaj A]] | ||
| + | [[Category: Houser A]] | ||
| + | [[Category: Noreng S]] | ||
| + | [[Category: Posert R]] | ||
Current revision
Full-length human ENaC ECD
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